The objective of this research is to elucidate the mechanism of action of insecticides on the nerve membrane which is the most critical target site of a variety of insecticides. Sophisticated electrophysiological techniques developed in our laboratory for the study of insecticides will be fully utilized, including intracellular microelectrode, voltage clamp and intracellular perfusion. The insecticides used for this study are DDT and its analogs and derivatives, and a variety of synthetic pyrethroids. The proposed study may be divided into three large categories. One is the detailed ionic mechanism of action of insecticides on the nerve membrane ionic channels. Kinetic analysis will be performed using Hodgkin-Huxley formulation and the role of membrane surface charges and dipole potential in the toxic actions of insecticides will be explored. The second project is concerned with the mechanism of action of insecticides on synaptic transmission. The third project involves the establishment of the true structure-activity relationship of insecticides by comparison of the direct action on the nerve (target site) as a measure of activity. These studies will provide the basis for the molecular mechanism of action of insecticides and clues to improvement of the existing insecticides.